Neural mechanisms of dystonia: evidence from a 2-deoxyglucose uptake study in a primate model of dopamine agonist-induced dystonia.
The neural mechanisms that mediate dystonia were investigated in a novel experimental primate model of dopamine agonist-induced dystonia. This condition was produced by long-term (15 months) dopamine agonist therapy of a macaque monkey that had been rendered hemiparkinsonian by unilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into the right common carotid artery. The 2-deoxyglucose (2-DG) metabolic mapping technique was applied to the animal during the expression of active unilateral dystonia, and regional brain uptake of 2-DG was assessed autoradiographically. The results demonstrate that dystonia is associated with marked increases in 2-DG uptake in the constituent nuclei of the basal ganglia (caudate nucleus, putamen, medial and lateral segments of the globus pallidus) and in the subthalamic nucleus, but decreased uptake in the structures that receive output of the basal ganglia (ventral anterior/ventral lateral thalamic complex and lateral habenula). Based on these findings it is suggested that dystonia is characterized by increased activity in the putaminopallidal and pallidosubthalamic pathways, and decreased activity in the subthalamopallidal and pallidothalamic pathways.
Mitchell
I J
IJ
Department of Cell and Structural Biology, School of Biological Sciences, University of Manchester, England.
Luquin
R
R
Boyce
S
S
Clarke
C E
CE
Robertson
R G
RG
Sambrook
M A
MA
Crossman
A R
AR
D000818:Animals; D001058:Apomorphine / Q000009:adverse effects* / Q000627:therapeutic use; D003837:Deoxy Sugars / Q000493:pharmacokinetics*; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D004421:Dystonia / Q000139:chemically induced* / Q000378:metabolism; D020267:MPTP Poisoning; D008252:Macaca fascicularis; D008297:Male; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000150:complications
D003837:Deoxy Sugars; D003847:Deoxyglucose; D001058:Apomorphine